Search Results (622)

Sulfur(VI) fluoride exchange (SuFEx) chemistry is a powerful click reaction for modular synthesis, distinguished by high chemoselectivity, broad functional-group tolerance and the formation of robust sulfur(VI)-based linkages. These attributes are particularly valuable for polymer functionalization, as S(VI)–F handles on either the polymer or the modifier enable covalent coupling under controlled conditions. This review spans SuFEx-mediated post-polymerization modification and architectural control of synthetic polymers, surface, interfacial and porous-material functionalization, and SuFEx-based conjugation and covalent capture in natural and sequence-defined biopolymers. Across these contexts, we compare the advantages, supporting mechanistic and analytical evidence, current limitations and future opportunities of SuFEx-enabled polymer functionalization. Full article

Background/Objectives: Antibody selection is critical for advancing pretargeted PET imaging toward clinical translation. This study directly compared two clinically approved anti-HER2 antibodies—trastuzumab and pertuzumab—within an identical pretargeting system, utilizing the specific chemical ligation between tetrazine and trans-cyclooctene (TCO) via the inverse electron-demand Diels–Alder (IEDDA) cycloaddition. Methods: In HER2-positive SKOV3 tumor-bearing mice, TCO-conjugated antibodies were administered 1–13 days prior to injection of a fluorine-18-labeled tetrazine probe ([¹⁸F]PEG₁₂-Tz). Results: Both strategies enabled high-contrast imaging, overcoming the kinetic mismatch between slow-clearing antibodies and the short-lived ¹⁸F isotope. Distinct profiles were observed: pertuzumab-TCO yielded higher tumor uptake and a broader imaging window (3–13 days), whereas trastuzumab-TCO resulted in lower uptake and a narrower window (1–5 days). These differences are not affinity-driven, as both conjugates showed similar Kd values (~11–14 nM). Instead, pertuzumab-TCO’s superiority stems from a dual mechanism: (1) slower cellular internalization (65.1% vs. 94.0% at 60 min) preserves surface TCO for click reaction; and (2) markedly slower blood clearance (t_1/2β = 285.9 h vs. 106.0 h) ensures sustained bioavailability and tumor extravasation. Conclusions: This head-to-head evaluation demonstrates that epitope-dictated internalization and clearance are decisive parameters for antibody selection, providing a mechanism-based framework for optimizing pretargeted imaging. Full article

To develop self-healing polyurethane materials with high transparency and superior mechanical performance, in this work, the poly(thiourethane) elastomers were prepared by incorporating the dynamic thiourethane bonds via thiol–isocyanate click reaction, followed by the addition of 1-(3-aminopropyl)imidazole (IZ), 3-hydroxypyridine (HP), and 2,4-diamino-6-hydroxypyrimidine (HPM) as ligands to produce three different polyurethane networks (named PTU-IZ, PTU-HP, and PTU-HPM). Zinc chloride (ZnCl₂) was further introduced to construct metal-coordinated crosslinking networks, recorded as PTU-IZ-Zn, PTU-HP-Zn, and PTU-HPM-Zn, respectively. The effects of ligands and Zn²⁺ coordination on the materials’ optical transmittance, mechanical properties, self-healing capability, and reprocessability were systematically investigated. The results demonstrate that HPM and Zn²⁺ will facilitate the formation of more effective crosslinking, which significantly enhances the mechanical properties of PTU-HPM from 4.61 MPa up to 9.04 MPa (PTU-HPM-Zn), while maintaining high transparency (89.0% light transmittance at 650 nm). Self-healing tests reveal that the PTU-HPM-Zn scratches can fully repair within 4 h at 70 °C. Reprocessability tests demonstrate that the internal crosslinked network of the material undergoes reversible dissociation, enabling a topological transition from a crosslinked to a linear structure and thereby imparting excellent thermal reprocessability. This study provides novel insights for the design and fabrication of high-performance transparent self-healing polyurethane materials. Full article

Marine deck coatings suffer from premature failures such as wear thinning, flaking, and brittle cracking under repeated rolling, abrupt stopping/steering, and high shear loads of heavy equipment due to the imbalance of hardness, strength, toughness, and wear resistance. To address this issue, a rolling load-resistant coating system with an epoxy–amine/epoxy–thiol dual-crosslinked network was constructed using liquid polysulfide rubber (Lp-3) as the key crosslinking modifier, and the effect of Lp-3 content (0–2 wt%) on the comprehensive performance of the coating was systematically investigated. The results showed that the coating achieved the optimal synergy of properties at 1 wt% Lp-3 loading: Shore hardness reached 88.7 HD with the pencil hardness maintained at 8H, adhesion strength increased to 7.2 MPa, Taber abrasion loss significantly decreased to 14.8 mg, tensile strength rose from 5.5 MPa to 12.4 MPa, elongation at break nearly doubled, shear strength reached 10.2 MPa, and the failure mode transformed from brittle cleavage to ductile shear. Mechanistic analysis revealed that the terminal thiol groups of Lp-3 underwent a click reaction with epoxy groups, covalently embedding flexible polysulfide segments into the rigid epoxy network and forming Fe–S interfacial chemical bonds to enhance adhesion. The microphase separation, chain relaxation, and energy dissipation mechanisms effectively blunted crack propagation and alleviated stress concentration, while maintaining sufficient surface hardness and the continuity of the load-bearing skeleton. This work realizes the synergistic optimization of high strength, high toughness, strong adhesion, and excellent wear resistance for marine deck coatings and provides a new strategy and critical technical parameters for the design of functional coatings under heavy-duty dynamic service environments. Full article

Virtual hand clicking is a common interaction task within the peripersonal space of virtual environments (VEs). Based on the hand–eye coordination mechanism, this study adopts click offset, reaction time, movement time, consumed endurance, and subjective evaluation scales as indicators to investigate the spatial morphology of virtual hand clicking interfaces. Experiment 1 analyzed the impacts of spatial depth, upper limb length, and spatial region on interaction performance to define 3D interface geometry. Experiment 2 further explored the 3D interface’s spatial reference center and depth based on upper limb length proportions. Integrated experimental results reveal that the relatively favorable 3D interface for static single-handed clicking tasks adopts a field-curved spherical layout, with its spatial reference center positioned at the midpoint of the user’s right shoulder. The recommended interaction depth ranges from 0.618 to 0.764 times the user’s upper limb length (or a fixed value of 400 mm for general designs). Full article

The cysteine-based thiol–epoxy ‘click’ reaction is demonstrated as an efficient and practical approach for the synthesis of zwitterionic structures. The transformation employs unprotected cysteine, proceeds in aqueous media, and affords quantitative conversions. Notably, acid- and base-catalyzed conditions provide exclusive access to different cysteine-based thioether regioisomers in aqueous conditions. The pH-responsive behavior of the resulting zwitterions is further elucidated by NMR spectroscopy. Finally, the synthetic strategy is extended to the preparation of cysteine- and glutathione-functionalized polyethylene glycol polymers, showcasing its utility for the preparation of amino acid-/peptide-containing macromolecular materials. Full article

Glycoclusters are important molecular tools for studying carbohydrate–protein interactions. It is advantageous to derive glycoclusters from carbohydrate-based scaffolds. Modulating the chair conformation of the scaffolding monosaccharide between ⁴C₁ and ¹C₄ enables the variation in the spatial organisation of the resulting glycoclusters, allowing the consequences for carbohydrate recognition in biological systems to be studied. Recently, we introduced a xylose derivative capable of adopting two complementary chair conformations, which was conjugated to glycoligands via Suzuki–Miyaura cross-coupling to afford homobivalent glycoclusters. Here, we expand this approach by further exploring the potential of xylose as a conformationally ‘switchable’ carbohydrate scaffold. Two additional features were introduced, (i) alkyne groups to facilitate conjugation reactions through click chemistry, and (ii) orthogonal protection to enable the synthesis of heterobivalent glycoclusters in addition to homobivalent analogues. This strategy enabled the synthesis of a focused library of homo- and heterobilvalent glycoclusters, which were subjected to preliminary biological evaluation. Notably, inversion of the chair conformation of the xyloside scaffold exerted a significant effect on the potency of the respective compounds as inhibitors of mannose-specific bacterial adhesion. Full article

The rapid hemostasis of deep and irregular wounds is of great clinical significance. In this study, an injectable hemostatic hydrogel based on bioorthogonal conjugation was developed. This gel uses thrombin (TMB) as the hemostatic active substance and 4ARM-PEG-N₃ as the crosslinking agent, which undergo orthogonal conjugation via the classic azide–alkyne click reaction to form an injectable hydrogel (TMB-PEG). The resulting hydrogel exhibited a transparent, injectable gel state. TEM images revealed that the hydrogel comprised sheet-like structures and interwoven fibers with a diameter of approximately 100 nanometers. In a puncture bleeding wound model, hemostasis with the TMB-PEG hydrogel required only 25 s, with a blood loss of 1.9 ± 1.3 mg, both approximately one-sixth of that of the control group. Moreover, the hemostatic performance of the TMB-PEG hydrogel was far superior to that of three other commonly used hemostatic materials. Furthermore, cephalosporin antibiotics were conjugated to the hemostatic gel via orthogonal reactions, endowing it with significant broad-spectrum antibacterial activity, achieving over 99% antibacterial efficacy against both Gram-negative and Gram-positive bacteria. Full article

Background/Objectives: Resistant pathogenic bacteria and fungi are a growing problem worldwide; therefore, the discovery of new active ingredients is an important challenge for which the functionalization of natural terpenes with biologically active heterocycles can provide a basis. To reach this goal, a series of 1,4-disubstituted-1,2,3-triazole conjugates was designed and synthesized starting from commercially available α-santonin. Methods: The key azido derivative intermediate was prepared according to literature procedures via Michael addition between dehydrosantonin and the TMSN₃/AcOH/Et₃N system at its highly reactive α-methylene-γ-lactone motif. Subsequently, the obtained azide was applied to regioselective Huisgen 1,3-dipolar cycloaddition reaction with a wide range of terminal alkynes bearing N-, S- and O-heterocycles. These include pyridine, pyrimidine, purine, quinoline, indol, or coumarin to afford the sesquiterpene–heterocycle chimaeras. All triazole conjugates were screened for in vitro antiproliferative activity by MTT assay against HeLa, MDA-MB231, SiHa, MCF-7 and A2780 human cancer cell lines compared with fibroblast cells (NIH/3T3) to check their cytotoxicity and antimicrobial effects on two Gram-positive (B. subtilis, S. aureus) pathogenic bacteria, two Gram-negative (E. coli and P. aeruginosa) pathogenic bacteria, and two yeasts (C. krusei and C. albicans). Results: The results indicated that most of the examined compounds expressed weak activity against human cell lines, while some of them showed moderate activity against S. aureus (up to 99% inhibition at 100 µg/mL conc.), C. krusei (up to 51% inhibition at 10 µg/mL conc.) and C. albicans (up to 52% inhibition at 10 µg/mL conc.). Conclusions: Further structural modification of the best, selective antibacterial and antifungal compounds may open the possibility to the development of effective natural sesquiterpene-based selective antimicrobial agents. Full article

Scaffolds designed for mechanically demanding soft tissue engineering applications should integrate mechanical support, efficient mass transfer, and good cellular compatibility. This work presents a one-pot method based on “radical-free click chemistry + carbodiimide coupling” to produce a double-network (DN) PEG–alginate cryogel. The PEG network is formed by a Michael addition reaction between thiol-based crosslinker and 8-arm PEG-acrylate. The second network is covalently crosslinked through EDC/NHS-mediated coupling of carboxyl groups in alginate and adipic acid dihydrazide (AAD). The subsequent freezing and gelation of the gel precursor at sub-zero temperatures results in an ice templated cryogel with an interconnected macroporous network. These cryogels demonstrate high elasticity, compressive modulus and rapid swelling equilibrium in aqueous environments, as well as controlled degradation under physiological conditions. Compared to the classical Ca²⁺ ion crosslinking systems, the covalent linking of the alginate in the double-network cryogel shows advantages in mechanical and structural stability. In addition, it is cell-compatible and allows culture of mesenchymal stem cells (MSCs) with homogeneous infiltration. Furthermore, the double-network cryogels supports chondrogenic differentiation of MSCs upon treatment with chondrogenic media or macrophage-conditioned media for a short period of time. These results indicate that crosslinking chemistry and polymer composition can be used to modulate the balance between mechanical performance and degradation behavior, while maintaining cytocompatibility and an interconnected macroporous network, thereby providing a scaffold design strategy for applications that require coordinated mechanical support and mass transfer, such as cartilage-related tissue engineering. Full article

UV-curable L(-)–borneol-functionalized antibacterial hydrogels for packaging fresh-cut banana and cherry tomato (UV-LBs) were designed from L(-)–borneol-functionalized polyurethane acrylate prepolymers (LB-PUAs) and thiol-functionalized PVA (PVA-SH) using a thiol-ene click reaction initiated by UV light. UV-LBs exhibit unique properties, including excellent thermal stability, high mechanical performance and quite high antibacterial efficiency. The initial thermal decomposition temperature (T_d5), tensile strength and elongation at break are in the range of 225–240 °C, 1.38–2.05 MPa and 44.4–68.6%, respectively. The antibacterial efficiency of UV-LBs against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Monilia albican (M. albican) can reach 67.4%, 75.6% and 83.7%, respectively. The storage time of packaged fresh-cut banana and cherry tomato can be extended from 12 h to 30 h and 4 d to 5 d, respectively. Full article

In this study, a non-typical luminescent organosilicone was synthesized through a click reaction and used as a cross-linker to cure hydroxyl-terminated dimethylsilicone oil at room temperature via the sol–gel process, followed by application as a coating on a glass surface. This organosilicone film functions effectively as a luminescent down-shifting (LDS) material. Additionally, the presence of methyl groups and voids in the structure imparts a low refractive index, allowing it to serve as an anti-reflective (AR) layer. Optical and structural analyses on organosilicone-coated glass samples were conducted, and the dual-functional layer was applied to the glass cover of a perovskite solar panel to evaluate its performance. The coating not only enhanced light transmission as an AR layer but also converted UV light into blue light, which was absorbed by the solar cell. The results indicated improved solar panel performance, particularly in short-circuit current (Isc), external quantum efficiency (EQE) in the UV wavelength range, and overall efficiency. Overall, this material is a promising candidate for solar panel applications owing to maximized UV absorption for LDS, preserved transparency of the top cover glass, and room-temperature gelation, which facilitates repair of the dual-functional coating. Full article

The rapid expansion of click chemistry reflects its transformative influence on contemporary drug discovery. This review highlights major advances in the application of click reactions within the kinetic target-guided synthesis (KTGS) paradigm for identifying potent inhibitors across a broad range of biological targets. KTGS constitutes a methodological shift that leverages the inherent dynamics of biomolecular systems, enabling biological targets to direct the in situ assembly of high-affinity bidentate ligands from a diverse repertoire of reactive building blocks. The review systematically classifies the principal bond-forming reactions that underpin effective inhibitor generation via KTGS. Collectively, it provides a comprehensive and scholarly analysis of how click-chemistry-enabled KTGS is redefining drug discovery and expediting the development of next-generation therapeutics. Full article

Electrochemical biosensors integrated into wearable devices have revolutionized the technology in terms of health monitoring and diagnostic systems. However, when it comes to moving the devices from the laboratory to real-world environments, a critical problem emerges with the interface. The problem, in essence, is that biorecognition elements tend to lose their activity, delaminate, and drift when exposed to various environmental stresses. The traditional methods for the immobilization of the biorecognition elements result in receptors with random orientations, hydrolytically unstable bonds, and batch-to-batch variability, regardless of the method, including physisorption or non-selective covalent attachment, like using EDC/NHS. This review is organized around a comparative question: which limitations of classical immobilization strategies (physisorption, self-assembled monolayers used as passive anchoring platforms, and EDC/NHS coupling) can be resolved by click chemistry, which can be resolved by mechanistic features? Accordingly, CuAAC, SPAAC, IEDDA, and thiol-ene/yne photoclick reactions are discussed, not as an isolated catalog of ligations, but as complementary solutions to specific interfacial failure modes, including random bioreceptor orientation, hydrolytically vulnerable attachment, poor batch reproducibility, catalyst sensitivity, and the difficulty of functionalizing soft polymeric or textile substrates. In this framework, click chemistry is treated as a deterministic interface-engineering strategy that enables defined covalent fixation, programmable probe density, and improved mechanical and electrochemical robustness under wearable operating conditions. Full article

Monoacylglycerol lipase (MAGL) is a key regulator of lipid signaling networks implicated in tumor progression and represents an attractive anticancer target. To combine MAGL inhibition with potentially enhanced uptake by highly glycolytic cancer cells, we designed glycoconjugated analogs of a N-benzoylpiperidine MAGL inhibitor scaffold bearing a glucopyranose unit. An alkyne-functionalized benzoylpiperidine intermediate was prepared and coupled to azido sugars through a CuAAC “click” reaction to afford two triazole-linked glycoconjugates. In a colorimetric assay on human MAGL, the new compounds 17 and 18 inhibited the enzyme with IC₅₀ values of 43.3 and 68.8 μM, respectively, confirming compatibility with MAGL inhibition albeit with reduced potency versus reference triazole-substituted benzoylpiperidine 13 (IC₅₀ = 4.1 μM). In PANC-1 pancreatic cancer cells, both glycoconjugates were inactive in high-glucose medium, but displayed antiproliferative activity under low-glucose conditions (GI₅₀ 17 = 129 μM; GI₅₀ 18 = 12 μM), consistent with glucose-dependent uptake/competition. Overall, these first-in-class MAGL-targeting glycoconjugates provide a starting point for optimizing dual MAGL inhibition and metabolically driven cellular selectivity. Full article